ArticleProceedings of the National Academy of Sciences of the United States of America2011
Cell culture model that mimics drusen formation and triggers complement activation associated with age-related macular degeneration.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 138 papers.
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138 citing papers in PubMed, 197 citations in OpenAlex.
- Systematic Analysis of Plasma-Derived Extracellular Vesicle-Enriched Samples in Age-Related Macular Degeneration Reveals Oxidative Stress Linked to Altered Lipid and Protein Profiles.Journal of extracellular biology · 2026Article
- Murine models of neovascular AMD revisited: Mechanistic pathways, immune-metabolic crosstalk, and the impact of aging and sex.Experimental eye research · 2026Review
- Causal relationship between aspirin use and age-related macular degeneration.Eye (London, England) · 2026Article
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- Mitochondrial ROS in Retinal Neurodegeneration: Thresholds, Quality Control Failure, and Precision Therapeutic Windows.Biomolecules · 2026Review
- Choriocapillaris Flow Signal Deficits Are Associated With AMD Onset and Early Progression Over Three Years: ALSTAR2 Follow-Up.Investigative ophthalmology & visual science · 2026Article
- The roles of glycerophospholipids in the aging retina and age-related macular degeneration.Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie · 2026Review
- Age-Driven Lipid Remodeling Activates Lysosome-Mediated Plasma Membrane Repair.Research square · 2026Article
- Assessing mitochondrial phenotypes in a cybrid model of dry age-related macular degeneration.Molecular vision · 2026Article
- Systemic and Local Lipids in Nonhuman Primates With Drusen and Age-Related Maculopathies.Investigative ophthalmology & visual science · 2025Article
- Article
- Dysregulated lipid metabolism in a retinal pigment epithelial cell model and serum of patients with age-related macular degeneration.BMC biology · 2025Article
- Porcine Sub-Retinal Pigment Epithelium Deposits: A Model for Dry Age-Related Macular Degeneration With Comparison to Human Drusen.Investigative ophthalmology & visual science · 2025Article
- The association between the C-reactive protein-to-albumin-to-lymphocyte index and retinopathy: insights from a population-based study.Frontiers in nutrition · 2025Article
- Characterization of drusen formation in a primary porcine tissue culture model of dry AMD.Molecular therapy. Methods & clinical development · 2024Article
- Aberrant Lipid Metabolism and Complement Activation in Age-Related Macular Degeneration.Investigative ophthalmology & visual science · 2024Review
- The quantification of zebrafish ocular-associated proteins provides hints for sex-biased visual impairments and perception.Heliyon · 2024Article
- The Complement System as a Therapeutic Target in Retinal Disease.Medicina (Kaunas, Lithuania) · 2024Review
- Understanding the Impact of Polyunsaturated Fatty Acids on Age-Related Macular Degeneration: A Review.International journal of molecular sciences · 2024Review
- CFH Haploinsufficiency and Complement Alterations in Early-Onset Macular Degeneration.Investigative ophthalmology & visual science · 2024Article
78 more citing papers are in PubMed but not listed here.
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Authors and funding
12 authors at 2 institutions in 1 country.
Funding
Abstract
We introduce a human retinal pigmented epithelial (RPE) cell-culture model that mimics several key aspects of early stage age-related macular degeneration (AMD). These include accumulation of sub-RPE deposits that contain molecular constituents of human drusen, and activation of complement leading to formation of deposit-associated terminal complement complexes. Abundant sub-RPE deposits that are rich in apolipoprotein E (APOE), a prominent drusen constituent, are formed by RPE cells grown on porous supports. Exposure to human serum results in selective, deposit-associated accumulation of additional known drusen components, including vitronectin, clusterin, and serum amyloid P, thus suggesting that specific protein-protein interactions contribute to the accretion of plasma proteins during drusen formation. Serum exposure also leads to complement activation, as evidenced by the generation of C5b-9 immunoreactive terminal complement complexes in association with APOE-containing deposits. Ultrastructural analyses reveal two morphologically distinct forms of deposits: One consisting of membrane-bounded multivesicular material, and the other of nonmembrane-bounded particle conglomerates. Collectively, these results suggest that drusen formation involves the accumulation of sub-RPE material rich in APOE, a prominent biosynthetic product of the RPE, which interacts with a select group of drusen-associated plasma proteins. Activation of the complement cascade appears to be mediated via the classical pathway by the binding of C1q to ligands in APOE-rich deposits, triggering direct activation of complement by C1q, deposition of terminal complement complexes and inflammatory sequelae. This model system will facilitate the analysis of molecular and cellular aspects of AMD pathogenesis, and the testing of new therapeutic agents for its treatment.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.